Natural bone is made up of a combination of inorganic elements, organic elements, and water. Inorganic elements, for example hydroxyapatite, make up approximately 70% of natural bone. Organic elements such as collagen type I make up approximately 20% of natural bone, and water makes up approximately 10%. Bone-forming cells, for example osteoblasts, produce and secrete or bind the organic elements. Further, non-collagen proteins, in particular osteocalcin, osteonectin, osteopontin, cytokine, growth inducing factor, proteoglycan and fat are present in natural bone.
Natural bone is constantly being degraded and regenerated, i.e. re-modeled. Osteogenesis, i.e., bone regeneration, originates from the bone itself, as observed for example during healing of bone fractures. Thus, natural bone has the capability to generate new functional bone.
In many cases, however, regeneration of natural bone is restricted. This may be caused by, for example, the extent of a bone defect or by different functional disorders, for example metabolic disturbances. Treatment of bone defects remains an important field, for example in orthopedics, repair to jaws, teeth and hands, surgery in connection with accidents, and facial surgery.
Bone defects have different origins, caused for example by cysts, atrophies, or tumors. Complicated comminute fractures, congenital deformities and loosening of implants also cause bone defects. There is increasing focus on the reconstruction of bone defects using suitable materials.
Bone graft substitute products on the market include InFuse® manufactured by Medtronic Sofamor Danek (Minneapolis, Minn.), and OP-1® Putty manufactured by Stryker Corporation (Kalamazoo, Mich.). These products are sold as kits that separately contain a bovine collagen scaffold and human recombinant Bone Morphogenic Protein (“rhBMP”) in a vial.
InFuse® uses rhBMP-2 which prior to implantation is soaked onto a sponge. OP-1® Putty is provided as two components: a vial containing one gram dry powder of bovine collagen, OP-1®, rhBMP-7, and another vial containing a putty additive of carboxymethylcellulose dry powder. Both components must be combined with saline to produce the implant. According to the OP-1® Putty package insert, 96% of patients treated with OP-1® Putty develop an immune response to the product.
With each of these products, the rhBMP component is applied to the scaffold is performed during the surgical procedure. Applying the rhBMP solution to the surface of the scaffold potentially results in a heterogeneous distribution of the rhBMP, i.e., certain areas of the scaffold will have a higher concentration of rhBMP than other areas of the scaffold. Further, as the surgeon is required to assemble the product in the operating room, there exists a risk of infection and inconsistent dosage from procedure to procedure.
There is a need for sterile homogeneous devices and compositions with high osteo-inductive or chondro-inductive activities and methods for treating bone and/or cartilage defects.